We have detected in crude cellular extracts a nuclear activity which cooperatively binds with the Rev protein to the Rev response element (RRE). This activity should be crucial for the in vivo function of Rev, the emergence from microbiological latency and the synthesis of mature virions during acute infection. Chromatographic analysis of the activity has determined it consists of at least four and possibly more than five separate proteins. One of the activities has been purified to the extent of five prominent bands on an SDS gel. We should soon be able to sequence and clone it. We have acquired sufficient physicochemical data about the other factors to facilitate their rapid cloning. We are now studying the factors by microinjecting them into mammalian cells along with Rev-dependent indicator genes. In related work we have studied the interaction of the Rev protein with the RRE. We have found that RRE elements determine the binding of Rev molecules subsequent to the first binding event. This precludes models for Rev/RRE binding which hold that all of the specificity is in the first binding event and that subsequent multimerization of Rev along an RNA molecule involves only non-specific recognition of RNA by Rev protein. Along slightly different lines, we have used subtractive cloning techniques to isolate clones of a number of cellular genes specifically up- and down-regulated by HIV infection. Surprisingly, HIV infection turns on Line-1, an endogenous human retroviral element, and switches off expression of S16 ribsomal protein. The mechanism and significance of these findings is currently being studied.